11β-alkynyl-estrenes and -estradienes, their production and pharmaceutical preparations containing them

Abstract

11β-substituted steroids of the formula ##STR1## wherein A and B together represent a second bond between the 6-position and 7-position carbon atoms, or, respectively, are each H; X is O, two H atoms or hydroximino; Z is the residue of a pentagonal or hexagonal ring which is optionally substituted and optionally saturated; R 1 is vinyl, C 3-7 -cyclo-1-alkenyl, phenyl, naphthyl or 5- or 6-membered heterocyclic aromatic having at least one N, O or S atom, each being unsubstituted or substituted by 1-3 halogen atoms, 1-3 C 1-4 -alkyl, C 1-4 -alkoxy, C 1-4 -acyl, C 2-10 -alkenyl, C 1-4 -acyloxy, phenyl, nitro, hydroxy, carboxy, cyanide, COOR 4 or amino optionally substituted by 1-2 C 1-4 -alkyl; R 2 is methyl or ethyl, R 3 is H, Cl or methyl; and R 4 is C 1-4 -alkyl optionally substituted by phenyl which itself is optionally substituted by C 1-4 -alkyl, C 1-4 -alkoxy, halogen or phenyl have valuable pharmacological properties.

What is claimed is: 
     
       1. An 11β-substituted steroid having a 5- or 6-membered D ring wherein rings A-C are of the formula ##STR9## wherein A and B together represent a second bond between the 6-position and 7-position carbon atoms, or are each H; X is O, two H atoms or hydroximino;   R 1  is vinyl, C 3-7  -cyclo-1-alkenyl, phenyl, naphthyl or a 5- or 6-membered aromatic ring having at least one N, O or S ring atom, each being unsubstituted or substituted by 1-3 halogen atoms, 1-3 C 1-4  -alkyl groups, C 1-4  -acyl, C 1-4  -alkoxy, C 2-10  -alkenyl, C 1-4  -alkanoyloxy, phenyl, nitro, hydroxy, carboxy, cyano, COOR 4  or amino optionally substituted by 1-2 C 1-4  -alkyl groups;   R 2  is methyl or ethyl,   R 3  is H, C1 or methyl; and   R 4  is C 1-4  -alkyl optionally substituted by phenyl which itself is optionally substituted by C 1-4  -alkyl, C-hd 1-4-alkoxy, halogen or phenyl.   
     
     
       2. A steroid according to claim 1, wherein the D ring is of the formula ##STR10## wherein R 5  /R 6  is ##STR11## --OR 7  /--(CH 2 ) m  --CH 2  --R 9  --OR 7  /--CH═CH(CH 2 ) k  --CH 2  --R 9 , or --OR 10  /--H, respectively, or R 5  and R 6  together are ##STR12## wherein R 7  is H or C 1-4  -acyl;   Y is H, alkyl, hydroxyalkyl, alkoxyalkyl or alkanoyloxyalkyl group wherein all alkyl portions have 1-4 carbon atoms;   R 8  is H, OH, C 1-4  -alkyl, C 1-4  -alkoxy or C 1-4  -alkanoyloxy;   R 9  is OH, CN, C 1-10  -alkoxy or C 1-4  -alkanoyloxy, optionally substituted by C 1-10  -alkoxy;   R 10  is H, C 1-10  -alkyl or C 1-10  -alkanoyl;   m is 0, 1, 2 or 3; and   k is 0, 1 or 2.   
     
     
       3. A steroid according to claim 1, wherein R 3 , A and B are each H. 
     
     
       4. A steroid according to claim 2, wherein R 3 , A and B are each H. 
     
     
       5. A steroid according to claim 1, wherein A and B together are a second bond and R 3  is H. 
     
     
       6. A steroid according to claim 2, wherein A and B together are a second bond and R 3  is H. 
     
     
       7. A steroid according to claim 1, wherein A and B together are a second bond and R 3  is C1. 
     
     
       8. A steroid according to claim 2, wherein A and B together are a second bond and R 3  is C1. 
     
     
       9. A steroid according to claim 1, wherein A and B together are a second bond and R 3  is methyl. 
     
     
       10. A steroid according to claim 2, wherein A and B together are a second bond and R 3  is methyl. 
     
     
       11. A steroid according to claim 2, wherein k is 0 or 1. 
     
     
       12. A steroid according to claim 1, wherein the alkenyl substituent of R 1  is branched or straight chained C 2-6  -alkenyl. 
     
     
       13. A steroid according to claim 1, wherein the halogen substituent of R 1  is C1 or F. 
     
     
       14. A steroid according to claim 1, wherein R 1  is cyclo-1-pentene or cyclo-1-hexene. 
     
     
       15. A steroid according to claim 1, wherein R 1  is substituted or unsubstituted phenyl, 1-naphthyl, 2-naphthyl, 2- or 3-furyl, 2- or 3-thienyl, 2-, 3- or 4-pyridyl, oxazolyl, thiazolyl, pyrimidinyl, pyridazinyl, pyrazinyl or 2-tetrazolyl. 
     
     
       16. A steroid according to claim 1, wherein said steroid is 17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(phenyl)ethynyl]estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-dimethylamino-phenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-methoxyphenyl)-ethynyl]-4-estren-3-one,   1α -(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-cyanophenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-acetylphenyl)-ethynyl)]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-acetylphenyl)-ethynyl]-4,6-estradien-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(4-methoxyphenyl)-ethynyl]-4,6-estradien-3-one   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(2-thienyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(3-thienyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(5-formyl-2-thienyl)-ethynyl)]-4-estren-3-one   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(3-pryridinyl)ethynyl[-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(4-pryridinyl)ethynyl]-4-estren-3-one   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(5-acetyl-2-thienyl)-ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β(2-phenylethynyl)-4,6-estradien-3-one, 17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(5-isopropoxycarbonyl-2-furyl)ethynyl]-4,6-estradien-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(3-nitrophenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(2-nitrophenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(2-methoxyphenyl)-ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(p-tolyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(o-tolyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(5-isopropoxycarbonyl-2-furyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(4-fluorophenyl)-ethynyl]-4,6-estradien,3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(4-isopropylphenyl)-ethynyl]-4,6-estradien-3-one,   17α-[2-(4-Methoxyphenyl)-ethynyl]-4-estrene[17(β-1')-spiro-5']-2',5'-dihydrofuran-3-one,   1β -[2-Tolyl)ethynyl]-4-estrene[17 (β-1')spiro-5']-2',5'-dihydrofuran-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-(3-methylbut-1-yn-3-enyl)-4,6-estradien-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(3-dimethylamino-phenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(m-tolyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β[2-(3,5-dimethylphenyl)-ethynyl]-4-estren-3-one,   17α-(3-Methoxymethoxyprop-1(Z)-enyl)-17β-hydroxy-11β-[2-(2-methoxyphenyl)ethynyl]-4-estren-3-one,   17α-(3-Hydroxyprop-1(Z)-enyl)-17β-hydroxy-11β-[2-(3-methoxyphenyl)ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(3-acetylphenyl)-ethynyl]-4-estren-3-one,   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(1-naphthyl)ethynyl]-4-estren-3-one, or   17α-(Prop-1-ynyl)-17β-hydroxy-11β-[2-(3-methoxyphenyl)-ethynyl]-4-estren-3-one.   
     
     
       17. A pharmaceutical compositon comprising a compound of claim 1 and a pharmaceutically acceptable carrier. 
     
     
       18. A method of post-coital birth control in a female patient comprising administering an effective amnount of a compound of claim 1 to a patient in need thereof. 
     
     
       19. A method for achieving an antiglucocorticoidal effect in a patient, comprising administering an effective amount of a coumpound of claim 1 to a patient in need thereof. 
     
     
       20. A method for achieving an antimineralocorticoidal effect in a patient, comprising administering an effective amount of claim 1 to a patient in need thereof.